ArticleCancer research2009
TrkBT1 induces liver metastasis of pancreatic cancer cells by sequestering Rho GDP dissociation inhibitor and promoting RhoA activation.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.Frontiers in neuroscience · 2022Pooled it
- Identification of Genes Associated with Liver Metastasis in Pancreatic Cancer Reveals PCSK6 as a Crucial Mediator.Cancers · 2022Article
- Adenocarcinomas of the Lung and Neurotrophin System: A Review.Biomedicines · 2022Review
- Oncogenic role of a developmentally regulatedScience advances · 2022Article
- Understanding the development of oral epithelial organs through single cell transcriptomic analysis.Development (Cambridge, England) · 2022Article
- A subtype of oral, laryngeal, esophageal, and lung, squamous cell carcinoma with high levels of TrkB-T1 neurotrophin receptor mRNA.BMC cancer · 2019Article
- Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma.Scientific reports · 2018Article
- Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity.Clinical & experimental metastasis · 2017Article
- Neurogenin 3 is regulated by neurotrophic tyrosine kinase receptor type 2 (TRKB) signaling in the adult human exocrine pancreas.Cell communication and signaling : CCS · 2016Article
- Article
- Novel Insights into the Roles of Rho Kinase in Cancer.Archivum immunologiae et therapiae experimentalis · 2016Review
- Tropomyosin-related kinase B/brain derived-neurotrophic factor signaling pathway as a potential therapeutic target for colorectal cancer.World journal of gastroenterology · 2016Review
- Article
- Eukaryotic Translation Initiation Factor 5A (EIF5A) Regulates Pancreatic Cancer Metastasis by Modulating RhoA and Rho-associated Kinase (ROCK) Protein Expression Levels.The Journal of biological chemistry · 2015Article
- RhoGDI deficiency induces constitutive activation of Rho GTPases and COX-2 pathways in association with breast cancer progression.Oncotarget · 2015Article
- The Correlation Between RhoA Expression and Clinicopathological Characteristics in Gastric Cancer Patients After Curative Surgery.World journal of surgery · 2015Article
- Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells.Molecular carcinogenesis · 2015Article
- Two-dimensional culture of human pancreatic adenocarcinoma cells results in an irreversible transition from epithelial to mesenchymal phenotype.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.Drug design, development and therapy · 2015Review
- SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.PloS one · 2014Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Many genetic and molecular alterations, such as K-ras mutation and NF-kappaB activation, have been identified in pancreatic cancer. However, the mechanisms by which pancreatic cancer metastasizes still remain to be determined. Although we previously showed that the tropomyosin-related kinase B (TrkB) was significantly correlated with the development of liver metastasis, its function in pancreatic cancer metastasis remained unresolved. In the present study, we showed that overexpressed TrkB is an alternatively spliced transcript variant of TrkB (TrkBT1) with a unique COOH-terminal 12-amino acid sequence and is mainly localized in the cytoplasm. Our results showed that overexpression of Flag-tagged TrkBT1 but not a Flag-tagged TrkBT1 COOH-terminal deletion mutant (Flag-TrkBT1DeltaC) in nonmetastatic pancreatic cancer cells enhanced cell proliferation, promoted formation of colonies in soft agar, stimulated tumor cell invasion, and induced liver metastasis in an orthotopic xenograft mouse model of pancreatic cancer. TrkBT1 interacted with Rho GDP dissociation inhibitor (GDI) in vivo, but Flag-TrkBT1DeltaC did not. Furthermore, overexpression of Flag-TrkBT1 and knockdown of RhoGDI expression by RhoGDI short hairpin RNAs promoted RhoA activation, but Flag-TrkBT1DeltaC overexpression did not. Therefore, our results showed that TrkBT1 overexpression induces liver metastasis of pancreatic cancer and uncovered a unique signaling mechanism by which TrkBT1 sequesters GDI and activates RhoA signaling.
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